Deformation of dark solitons in a PT -invariant variable coefficients nonlocal nonlinear Schrödinger equation.

We derive dark and antidark soliton solutions of a parity-time reversal (PT) -invariant variable coefficients nonlocal nonlinear Schrödinger (NNLS) equation. We map the considered equation into a defocusing PT -invariant NNLS equation with a constraint between dispersion, nonlinearity, and gain/loss parameters. We show that the considered system is PT -invariant only when the dispersion and nonlinearity coefficients are even functions and gain/loss coefficient is an odd function. The characteristics of the constructed dark soliton solutions are investigated with four different forms of dispersion parameters, namely, (1) constant, (2) periodically distributed, (3) exponentially distributed, and (4) periodically and exponentially distributed dispersion parameter. We analyze in detail how the nonlocal dark soliton profiles get deformed in the plane wave background with these dispersion parameters.

Recommendations for screening and early detection of common cancers in India.

Cancers of the breast, uterine cervix, and lip or oral cavity are three of the most common malignancies in India. Together, they account for about 34% of more than 1 million individuals diagnosed with cancer in India each year. At each of these cancer sites, tumours are detectable at early stages when they are most likely to be cured with standard treatment protocols. Recognising the key role that effective early detection and screening programmes could have in reducing the cancer burden, the Indian Institute for Cytology and Preventive Oncology, in collaboration with the US National Cancer Institute Center for Global Health, held a workshop to summarise feasible options and relevant evidence for screening and early detection of common cancers in India. The evidence-based recommendations provided in this Review are intended to act as a guide for policy makers, clinicians, and public health practitioners who are developing and implementing strategies in cancer control for the three most common cancers in India.

Meta-analysis of the efficacy of cold coagulation as a treatment method for cervical intraepithelial neoplasia: a systematic review.

BACKGROUND: Cold coagulation is an ablative method for treatment of cervical intraepithelial neoplasia (CIN). Despite reports of efficacy against all grades of CIN (CIN1-3), cold coagulation has been infrequently used since the 1980s, and was absent from the recent Cochrane review on CIN treatment. OBJECTIVES: To provide a systematic review of cold coagulation efficacy and acceptability for CIN treatment through meta-analysis of clinical reports and a randomised control trial. SEARCH STRATEGY: A literature search in PubMed, Web of Science, EMBASE, and regional databases yielded 388 papers. Title, abstract and/or reference list review identified 22 papers describing cold coagulation treatment of CIN, with 13 providing adequate data for inclusion in the meta-analysis. SELECTION CRITERIA: Publications or conference abstracts describing original data (number of women treated, followed up and cured, provider type, cure definition) were retained. No language or publication date limitations were imposed. DATA COLLECTION AND ANALYSIS: Data extracted from 13 studies were pooled, and statistical analyses of proportion cured were conducted with data stratified by lesion grade and study region. MAIN RESULTS: Among 4569 CIN patients treated with cold coagulation, summary proportion cured of 96% [95% confidence interval (CI) 92-99%] and 95% (92-98%) were obtained for CIN1 and CIN2-3 disease, respectively. Side-effects and adverse effects were infrequent, and fertility was not impaired. CONCLUSIONS: Cold coagulation CIN cure rates were comparable to those of other excisional and ablative methods. Cold coagulation is indicated for all grades of CIN, is safe, quick and acceptable, and may be of particular relevance for use in resource-limited settings.

Assessment of Registry-Based Surveillance Statistics Used for Cancer Control in the Dindigul District in South India.

Background: Cancer incidence rates from the Dindigul district were lower by 50% than Chennai in Tamil Nadu for most cancers. This study describes the cancer surveillance statistics and provides an assessment of missing cases from routine registration in the Dindigul Ambilikkai Cancer Registry (DACR), covering a predominantly rural population in the Dindigul district. Method: A total of 21,214 incident cancers in the DACR during 2003-2017 were examined for this study. Cancer registration was carried out by active case-finding following standard international norms. A total of 12,541 incident cancers registered during 2003-2012 and followed through 2014 were used to estimate survival. Data on follow-up were obtained through a mixture of active and passive methods. Survival probability was estimated by actuarial methods. A random survey carried out independently was used to assess the quality of case ascertainment. Results: The age-standardized rate (ASR) per 100,000 population was higher among women (76.2) than men (61) in 2013-2017, with both sexes reporting a 17% increase compared to 2003-2007. The most common cancers were cervix (ASR,18.5) and female breast (ASR,17.1), with percentage changes of -19% and +46.1%, respectively. Lung cancer (ASR, 5.5) was top among men with an increasing trend (+57.1%). The percent change in ASR of mouth cancer showed opposite trends among men (+24.3%) and women (- 21.4%). The ASR of colorectal cancers almost doubled among men between 2003-2007 and 2013-2017 (3.9; +94.7%). The 5- and 10-year absolute survival for all cancers were 31% and 20%, respectively. Out of 365 incident cancers that occurred during 2003-2010 in the surveyed areas, 310 (84.9%) were already registered in the DACR, while 55 were newly identified from the survey (15.1%). Inadequate coverage of sources outside the Dindigul district was significant (P = .002), with the highest number of missed cases from hospitals under nongovernment sectors (58.3%). Underascertainment was higher among cancer patients living in hilly regions (60%) and border areas (47.4%) than in core regions (P = .05). Conclusion: Because of an enacted government order making cancer a notifiable disease, the registry-based cancer surveillance could be extended, covering a population of 80 million in a cost-effective manner with enhanced coverage and systematic evaluation of cancer-screening programs.

Can visual cervical screening be sustained in routine health services? Experience from Mali, Africa.

OBJECTIVE: To assess the feasibility of sustaining visual cervical screening and treatment services in Mali, and to evaluate their performance and impact in improving the provision of cervical cancer control, following an initial cross-sectional study. DESIGN: Descriptive study. SETTING: Bamako area, Mali. POPULATION: Women aged 30-59 years. METHODS: Routine visual screening and treatment services were organised through two hospitals and 14 health centres. Patients with positive visual screening tests underwent colposcopy and/or directed biopsies, and ablative or surgical excision treatment was offered to those with cervical intraepithelial neoplasia (CIN). MAIN OUTCOME MEASURES: Test positivity, detection and treatment rates for CIN and the sustainability of screening services. RESULTS: Of the 14,141 women screened, 1682 (11.9%) were positive and were referred for further investigations and treatment. Over 75% of the screen-positive women underwent colposcopy and/or biopsy. CIN 1 was detected in 383 women, CIN 2 in 88, CIN 3 in 37 and invasive cervical cancer in 497. More than 80% of women with CIN and 35% of those with invasive cancer received treatment. The test performance characteristics and treatment coverage of routine screening were similar to those observed in the preceding cross-sectional study. CONCLUSION: Visual screening and treatment services are sustainable and effective in improving cervical cancer control provision by health services in Bamako, Mali. It is essential to organise and sustain several point-of-care services in order to extend cervical cancer prevention in low-income African countries.

Influence of Sn4+ ion on band gap tailoring, optical, structural and dielectric behaviors of ZnO nanoparticles.

II-VI semiconductors are being attracted due to excellent optical and electronic behaviors when they utilize for device fabrication. Among II-VI semiconductors, Zinc oxide finds cutting-edge results for various applications with a lack of toxicity. Sn4+ ion incorporated ZnO nanoparticles have been synthesized using a soft chemical route and characterized for the investigation of properties like structural, morphological, elemental, optical and dielectric responses. The prepared ZnO had a hexagonal structure and the particles size reduces by the influence of Sn4+ ion: this reduction rate increases for the increase of doping ratio. The average particles size was estimated within 24-34 nm. TEM, HRTEM and SEM results corroborate the structural aspects noticed using XRPD study. UV-vis study results showed that a blue shift on the optical band gap was received for high doping concentration (10 at.%) of Sn4+. PL peaks were observed in the UV region for 0 at.% and 2 at.% Sn4+ doped ZnO nanoparticles, and the peak position was shifted from UV to violet and blue region for 10 at.% Sn4+ doped ZnO nanoparticles. The dielectric permittivity was reduced due to the addition of Sn4+ ions. The AC conductivity was increased for higher doping concentrations. The Sn4+ ion incorporated ZnO nanoparticles shall be useful for various applications including LED fabrication for blue emission and also it is suitable to act as a buffer material in solar panel.

Clinical trials of cancer screening in the developing world and their impact on cancer healthcare.

Several research and training initiatives were organized by the International Agency for Research on Cancer (IARC) in collaboration with national institutions in countries such as Angola, Brazil, Burkina Faso, China, Republic of Congo, Guinea, India, Mali, Mauritania, Nepal, Niger, Peru, Tanzania and Thailand among others, to address feasible and effective means of early detection and prevention of cervical, breast and oral cancers. The impact of these activities, that involved over 600 000 participants and more than 1200 healthcare personnel trained on strengthening the local health services in terms of infrastructure, human resources and service delivery aspects in host countries and other regions, is addressed here. These studies, inbuilt in appropriate health services platforms, have resulted in the development and sustenance of several continuing point of care services of screening and treatment in most host countries, particularly in sub-Saharan Africa, and have catalysed regional early detection programmes in India, China and Thailand. The IARC collaborative studies have evolved into major focal points of training and extending services in many countries. The large evidence base, resulting from ours and other studies is likely, in due course, to facilitate much wider scaling up of screening and treatment services through organised programmes.

Trends in cancer incidence in Chennai city (1982-2006) and statewide predictions of future burden in Tamil Nadu (2007-16).

BACKGROUND: This paper investigates cancer trends in Chennai and predicts the future cancer burden in Chennai and Tamil Nadu state, India, using data on 89 357 incident cancers from the Chennai registry during 1982-2006, published incidence rates from the Dindigul Ambilikkai Cancer Registry during 2003-06 and population statistics during 1982-2016. METHODS: Age-specific incidence rates were modelled as a function of age, period and birth cohort using the NORDPRED software to predict future cancer incidence rates and numbers of cancer cases for the period 2007-11 and 2012-16 in Chennai. Predictions for Tamil Nadu state were computed using a weighted average of the predicted incidence rates of the Chennai registry and current rates in Dindigul district. RESULTS; In Chennai, the total cancer burden is predicted to increase by 32% by 2012-16 compared with 2002-06, with 19% due to changes in cancer risk and a further 13% due to the impact of demographic changes. The incidence of cervical cancer is projected to drop by 46% in 2015 compared with current levels, while a 100% increase in future thyroid cancer incidence is predicted. Among men, a 21% decline in the incidence of oesophageal cancer by 2016 contrasts with the 42% predicted increase in prostate cancer. The annual cancer burden predicted for 2012-16 is 6100 for Chennai, translating to 55 000 new cases per year statewide (in Tamil Nadu). Breast cancer would dislodge cervical cancer as the top-ranking cancer in the state, while lung, stomach and large bowel cancers would surpass cervical cancer in ranking in Chennai by 2016. CONCLUSION: In order to tackle the predicted increases in cancer burden in Tamil Nadu, concerted efforts are required to assess and plan the infrastructure for cancer control and care, and ensure sufficient allocation of resources.

Global oral health inequalities in incidence and outcomes for oral cancer: causes and solutions.

The mouth and oropharynx are among the ten most common sites affected by cancer worldwide, but global incidence varies widely. Five-year survival rates exceed 50% in only the best treatment centers. Causes are predominantly lifestyle-related: Tobacco, areca nut, alcohol, poor diet, viral infections, and pollution are all important etiological factors. Oral cancer is a disease of the poor and dispossessed, and reducing social inequalities requires national policies co-ordinated with wider health and social initiatives - the common risk factor approach: control of the environment; safe water; adequate food; public and professional education about early signs and symptoms; early diagnosis and intervention; evidence-based treatments appropriate to available resources; and thoughtful rehabilitation and palliative care. Reductions in inequalities, both within and between countries, are more likely to accrue from the application of existing knowledge in a whole-of-society approach. Basic research aimed at determining individual predisposition and acquired genetic determinants of carcinogenesis and tumor progression, thus allowing for targeted therapies, should be pursued opportunistically.

Research on cancer prevention, detection and management in low- and medium-income countries.

The burden of cancer in low- and medium-income countries (LMIC) is expected to increase in the next decades. The application of current knowledge and results of research in key areas would contribute to limit the impact of this phenomenon. Opportunities for research on cancer prevention in LMIC include investigating specific circumstances of exposure to known carcinogens and to agents which are not prevalent in other regions, as well as interactions among carcinogens and between genetic and environmental factors. Early detection both by screening and early clinical diagnosis represents an important component of cancer control in LMIC. Research has been carried out to identify effective and sustainable approaches for early detection of cervical cancer through human papillomavirus testing and visual tests and of oral cancer through visual inspection. For other important neoplasms such as breast cancer, on the other hand, no effective low-cost screening methods are currently available. Downstaging represents a potentially important approach for cancer control and a priority area for future research. Studies addressing the efficacy of treatment protocols, country-specific cost-effectiveness of various interventions and the clinical utility and cost-effectiveness of innovative heath care and communication technologies represent the priority for clinical cancer research.

Intramolecular proton transfer effects on 2,6-diaminopyridine.

The photophysical behaviour of 2,6-diaminopyridine (DAP) has been studied in solvents of different polarity, pH, beta-cyclodextrin (beta-CD) and compared with 2-amino pyridine (2AP). The inclusion complex of both molecules with beta-CD are analysed by UV-visible, fluorimetry, FT-IR, (1)H NMR, SEM and AM1 methods. The solvent studies shows i) DAP gives more red shifted absorption and emission maxima than 2AP molecule and ii) addition of amino group in 2AP effectively increase the resonance interaction in the pyridine ring. A regular red shift observed in acidic pH solutions suggests intramolecular proton transfer (IPT) present in both molecules. beta-CD studies indicates i) in pH approximately 7, a regular red shifted absorption and emission maxima observed in AP molecules suggests pyridine ring encapsulated in to the beta-CD cavity (1:1 inclusion complex formed) and ii) in pH approximately 1, a blue shifted absorption maxima noticed in 2AP, is due to protonated amino group deeply encapsulated in to the hydrophobic part of the beta-CD cavity.

Performance of colposcopy in five sub-Saharan African countries.

OBJECTIVE: The performance of colposcopy provided in a screening study in five African countries was evaluated. DESIGN: Cross-sectional study. SETTING: Burkina Faso, Congo Brazzaville, Guinea Conakry, Mali and Niger. POPULATION: Women aged 25-59 years. METHODS: A total of 29 294 women participated in a cervical screening study in the five study sites, and newly trained local doctors performed colposcopy and directed biopsies as indicated. Using meta-analytical tools, four measures of colposcopy performance at different thresholds of colposcopic abnormalities were assessed. Sources of heterogeneity were also assessed. MAIN OUTCOME MEASURES: Proportions of women receiving biopsies, adequate biopsies and women diagnosed with cervical intraepithelial neoplasia (CIN). RESULTS: Among 28 553 women with satisfactory colposcopy, 3101 had a colposcopic diagnosis of probable low-grade or worse lesions and 1128 probable high-grade or worse lesions. Overall, the measures that reached the set standards were proportion of biopsy taken at colposcopy threshold of probable high-grade or worse lesions (95%, 95% CI 90-100%) and proportion of adequate biopsy samples. The set standards were not met for the proportions of women diagnosed with CIN at different colposcopic abnormality thresholds. Detection of CIN2 or worse lesions increased with increasing colposcopic abnormality. CONCLUSIONS: The performance of colposcopy in some of the African sites studied was comparable to that previously observed in other studies. With appropriate training, monitoring, continuing practice and quality assurance, adequate standards of colposcopy can be attained in sub-Saharan Africa.

Preliminary X-ray crystallographic analysis of ornithine acetyltransferase (Rv1653) from Mycobacterium tuberculosis.

The gene product of open reading frame Rv1653 from Mycobacterium tuberculosis is annotated as encoding a probable ornithine acetyltransferase (OATase; EC 2.3.1.35), an enzyme that catalyzes two steps in the arginine-biosynthesis pathway. It transfers an acetyl group from N-acetylornithine to L-glutamate to produce N-acetylglutamate and L-ornithine. Rv1653 was crystallized using the sitting-drop vapour-diffusion method. The native crystals diffracted to a resolution of 1.7 A and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 60.1, b = 99.7, c = 155.3 A. The preliminary X-ray study showed the presence of a dimer in the asymmetric unit of the crystals, which had a Matthews coefficient V(M) of 2.8 A(3) Da(-1).

HPV vaccination: the promise & problems.

Four-fifths of the cervical cancer burden in the world is experienced in developing countries. HPV genotypes 16 and 18 account for 70 per cent of cervical cancers and currently available vaccines targeting these two types confer a high degree of protection against HPV 16/18 infection and related cervical precancerous lesions. However, widespread implementation of HPV vaccination programs are challenged by the unaffordable high costs of the vaccines and the lack of effective vaccine delivery platforms for sexually naïve girls. Other unresolved issues include long-term protection, cross-protection against HPV types not included in the vaccine and whether booster doses will be needed. Sensitivities associated with a vaccine preventing a sexually transmitted infection in girls, lack of awareness, public demand and political will, lack of coordination between cancer control, sexual and reproductive health and vaccine delivery services are additional challenges. Reduced costs, simple vaccine regimes and strengthening vaccine delivery platforms for adolescents should eventually facilitate HPV vaccine introduction in developing countries.

Completed suicide in adults of rural Kerala: rates and determinants.

BACKGROUND: India has witnessed a dramatic increase in suicide rates during the past few decades. The southern state of Kerala has been reporting the highest rates of suicide. Since suicide rates are estimated from death registries, they are likely to be under-reported because the civil registration system is incomplete and suicide deaths are poorly reported. METHODS: A cohort of 132 000 participants (age 35 years and above) in Thiruvananthapuram (erstwhile Trivandrum) district, Kerala was followed up for mortality from 1996 to 2005, after having filled-in a lifestyle questionnaire at baseline. The cause of death was based on verbal autopsy. Suicide methods were recorded and rates were estimated, and suicide risks were calculated according to several socioeconomic factors. RESULTS: During the follow up period, a total of 11 608 deaths, of which 385 were suicides (3.3% of total deaths), were registered. The overall suicide rate was 39.3/100 000 person-years among adults 35-90 years of age (men: 78/ 100000; women: 16.5/100000). The predominant methods of suicide were hanging, followed by poisoning and drowning. The suicide determinants were male gender, middle-age (40-60 years), Hindu, alcohol drinkers and secondary education level (< or = 7 years). Neither low socioeconomic level, living alone, nor being a married woman was associated with suicide risk. CONCLUSION: Suicide rates were consistent with the official rates of Thiruvananthapuram district (37/100 000). However, our study population did not include the 14-34-year-old age-group which represents more than 37% of all suicides and hence it is more likely that the official rates are under-reported. Determinants of suicide were in line with previous studies.

In vitro bioactivity, mechanical behavior and antibacterial properties of mesoporous SiO2-CaO-Na2O-P2O5 nano bioactive glass ceramics.

Bioactive ceramics, glasses and glass ceramics have the ability to enhance the bone formation and bond to surrounding tissue. In this study, we report on the synthesis of mesoporous nanobioactive glass ceramic with the modified composition of quaternary system 50% SiO2 - 26% Na2O - 20% CaO- 4% P2O5 (Ca/P: 5) [i.e.50S20C] by sol-gel method and succeeded by heat treatment. The as-dried sample was calcined at various temperatures such as 100 °C, 300 °C, 500 °C, 700 °C and 900 °C for 24 h.The weight loss measurement was carried out using Thermogravimetric (TG) analysis. The structural features were characterized by X-ray diffraction (XRD), Fourier transformed infrared spectroscopy (FTIR), Field Emission Scanning Electron Microscopy (FESEM) & Energy Dispersive Spectroscopy (EDS) analysis. The results revealed that the synthesized glass ceramic stabilized at higher temperature (700 °C and 900 °C)making more formation of the crystalline phase of sodium calcium silicate. The density and porosity measurements were carried out by using the Archimedes immersion method. The mechanical properties of the glass ceramic exhibit the compressive strength as69 MPa and 72 MPa for 700 °C and 900 °C, respectively. From the obtained results, we confirmed the calcined bioactive glass ceramic nanoparticles at 700 °C and 900 °C having a better crystallization, crystallite size with high surface area, high density, suitable porosity of mesoporous with dense microstructure and adequate mechanical properties. Furthermore, in vitro bioactivity character of calcined nanobioactive glass ceramics were studied by using an immersion of nanopowders into Stimulated Body Fluid (SBF) solution for two different time periods such as 7 and 14 days. After soaking the glass ceramic nanopowders in SBF, the structural and morphological changes were determined by using XRD, FTIR and FESEM & EDS analysis, respectively. The in vitro results exhibited that crystallization did not retard the samples bioactivity which indicates the increase of material bioactivity while calcining temperature was increased and it is used to fabricate tissue engineering scaffolds with sustained mechanical properties. Moreover, the enhanced bactericidal behavior of glass ceramic has also been studied. An antibacterial study revealed that the prepared bioactive glass ceramic show a significant effect on two bacteria E. coli and S. aureus.

An asymmetric dimer of beta-lactoglobulin in a low humidity crystal form--structural changes that accompany partial dehydration and protein action.

Dimeric lactoglobulin molecules exist in the open conformation at basic pH, whereas they exist in the closed conformation at acidic pH, after undergoing the Tanford transition around neutral pH. Orthorhombic crystals consisting of molecules in the open conformation, grown close to neutral pH, undergo a water-mediated transformation when the relative humidity around the crystals is reduced. The two subunits in the dimer are related by a crystallographic twofold axis in the native crystals while the dimer is asymmetric in the low humidity form. Interestingly, one of the subunits in the dimer in the low humidity form is in an open conformation while the other is in a closed conformation. This is the first observation of such an asymmetric dimer. A hydrogen bond between the side chains of Gln35 and Tyr42 exists and the side chain of Glu89 is substantially buried in the closed subunit of the asymmetric unit, as in other structures with molecules in the closed conformation. However, the closure of the EF loop is not complete; its conformation can be described as half-closed. A comparison of different crystal structures of beta-lactoglobulin indicates that the conformation of the loops in the molecule is substantially influenced by other factors such as crystal packing, the pH, and the composition of the medium, while the change in the conformation of the EF loop follows the Tanford transition. The mutual disposition of the two subunits in the low humidity form is halfway between those in the open and closed structures. The present work further demonstrates that structural changes that occur during partial dehydration could mimic those that occur during the action of proteins.

Synthesis of 3-(2-pyridyl)-2-substituted-quinazolin-4(3H)-ones as new analgesic and anti-inflammatory agents.

A new series of 3-(2-pyridyl)-2-substituted-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 2-hydrazino-3-(2-pyridyl)-quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material 2-hydrazino-3-(2-pyridyl)-quinazolin-4(3H)-one was synthesized from 2-aminopyridine. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. While the test compounds exhibited significant activity, compound 2-(1-ethylpropylidene)-hydrazino-3-(2-pyridyl)-quinazolin-4(3H)-one (AS2) showed moderate analgesic activity and compound 2-(1-methylbutylidene)-hydrazino-3-(2-pyridyl)-quinazolin-4(3H)-one (AS3) showed realistic anti-inflammatory activity when compared to the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic side effect when compared to aspirin.

Water-mediated variability in the structure of relaxed-state haemoglobin.

The crystal structure of high-salt horse methaemoglobin has been determined at environmental relative humidities (r.h.) of 88, 79, 75 and 66%. The molecule is in the R state in the native and the r.h. 88% crystals. At r.h. 79%, the water content of the crystal is reduced and the molecule appears to move towards the R2 state. The crystals undergo a water-mediated transformation involving a doubling of one of the unit-cell parameters and an increase in water content when the environmental humidity is further reduced to r.h. 75%. The water content is now similar to that in the native crystals and the molecules are in the R state. The crystal structure at r.h. 66% is similar, but not identical, to that at r.h. 75%, but the solvent content is substantially reduced and the molecules have a quaternary structure that is in between those corresponding to the R and R2 states. Thus, variation in hydration leads to variation in the quaternary structure. Furthermore, partial dehydration appears to shift the structure from the R state to the R2 state. This observation is in agreement with the earlier conclusion that the changes in protein structure that accompany partial dehydration are similar to those that occur during protein action.

A novel lysine-rich domain and GTP binding motifs regulate the nucleolar retention of human guanine nucleotide binding protein, GNL3L.

A variety of G-proteins and GTPases are known to be involved in nucleolar function. We describe here a new evolutionarily conserved putative human GTPase, guanine nucleotide binding protein-like 3-like (GNL3L). Genes encoding proteins related to GNL3L are present in bacteria and yeast to metazoa and suggests its critical role in development. Conserved domain search analysis revealed that the GNL3L contains a circularly permuted G-motif described by a G5-G4-G1-G2-G3 pattern similar to the HSR1/MMR1 GTP-binding protein subfamily. Highly conserved and critical residues were identified from a three-dimensional structural model obtained for GNL3L using the crystal structure of an Ylqf GTPase from Bacillus subtilis. We demonstrate here that GNL3L is transported into the nucleolus by a novel lysine-rich nucleolar localization signal (NoLS) residing within 1-50 amino acid residues. NoLS identified here is necessary and sufficient to target the heterologous proteins to the nucleolus. We show for the first time that the lysine-rich targeting signal interacts with the nuclear transport receptor, importin-beta and transports GNL3L into the nucleolus. Interestingly, depletion of intracellular GTP blocks GNL3L accumulation into the nucleolar compartment. Furthermore, mutations within the G-domains alter the GTP binding ability of GNL3L and abrogate wild-type nucleolar retention even in the presence of functional NoLS, suggesting that the efficient nucleolar retention of GNL3L involves activities of both basic NoLS and GTP-binding domains. Collectively, these data suggest that GNL3L is composed of distinct modules, each of which plays a specific role in molecular interactions for its nucleolar retention and subsequent function(s) within the nucleolus.